Intra- and Inter-operator variability in manual tumor segmentation: Impact on radionuclide therapy dosimetry

Abstract Purpose The aim was to quantify inter- and intra-observer variability in manually delineated lesion contours and the resulting impact on radionuclide therapy dosimetry. Methods Ten patients with hepatocellular carcinoma lesions treated with 90Y radioembolization (RE) and imaged with post-therapy 90Y PET/CT were selected for retrospective analysis. Three radiologists contoured 20 lesions manually on baseline multiphase contrast-enhanced MRIs and two of the radiologists re-contoured at two additional sessions. Contours were transferred to co-registered PET/CT-based 90Y dose-maps. Volume-dependent recovery-coefficients (RCs) were applied for partial volume correction when reporting mean absorbed dose. To understand how uncertainty varies with tumor size, we fit power models regressing relative uncertainty in volume and in mean absorbed dose on contour volume. Finally, we determined effects of uncertainty on tumor control probability (TCP), as calculated using logistic models developed in a previous report for lesions treated with RE. Results The average lesion volume ranged from 1.8 mL to 194.5 mL and the mean absorbed dose ranged from 23.4 to 1,629.0 Gy. The mean inter-observer Dice coefficient for lesion contours was significantly less than the mean intra-observer Dice coefficient (0.79 vs. 0.85, p < 0.001). Uncertainty in volume, as measured by the Coefficient of Variation (CV) ranged from 4.2% to 34.7% with a mean of 17.2%. For lesions > 8 mL, the CV in mean absorbed dose had an average value of 7.2% (range 1.5% to 12.6%) while for smaller lesions it was 21.7% (range 8.4 to 55.2%). The fitted uncertainty curves as a function of volume, v (in mL), were: %CV (volume) = 23.0* v-0.17 and %CV (mean dose) = 32.4* v-0.44. With this model for uncertainty, the mean change in TCP was 16.2% (maximum 48.5%). Conclusion Though we find relatively high inter- and intra-observer reliability overall, uncertainty in tumor contouring propagates into non-negligible uncertainty in dose metrics and outcome prediction for individual cases that should be considered in dosimetry-guided treatment.